Over the past few years, there has been an explosion of therapeutic advances for patients with non–small cell lung cancer (NSCLC) with molecular abnormalities or high levels of PD-L1 expression.
However, most patients with NSCLC do not have these targets, leaving platinum-based chemotherapy doublets—often in combination with angiogenesis inhibitors, such as bevacizumab (Avastin)—as standard treatment.
“The big thing is to not forget your chemotherapy backbones,” says Mary Jo Fidler, MD. “It is easy to jump to some of the immunotherapies or try to apply targeted agents but really, for the patient without a driver mutation and without the high expression of PD-L1, chemotherapy is the best option for them.”
Fidler, an associate professor of Medicine at Rush University Medical Center, discussed this patient population during the 2017 OncLive®
State of the Science Summit on Advanced Non–Small Cell Lung Cancer. In an interview at the meeting, she shared insight on research aiming to improve platinum-based doublet therapy and the role of chemotherapy for non-driver adenocarcinoma in the future.
OncLive: You spoke about patients with stage IV lung adenocarcinoma without driver mutations. What is important to highlight about these patients?
This talk was about systemic treatment of NSCLC in patients without drivers and without a high expression of the PD-L1 protein, which are still the bulk of patients who are coming through the door. We focused on how we got to platinum-doublet therapy as a cornerstone and ways to improve upon it. There were also studies on maintenance strategies, adding angiogenic agents, and studies adding EGFR
-targeted therapies to the backbone of chemotherapy.
In what ways are we improving upon platinum-doublet therapy?
If you look at the survival comparisons between 1 platinum doublet and another, we have made little progress and survival curves are overlapping. However, there are some subtleties and toxicities [between them], and there may be some subtleties in patient selection.
For example, nab-paclitaxel (Abraxane) may have a higher response rate in squamous cell patients. We hear a little bit about why these platinum doublets are not equal and how can we tease them out a little bit.
What do we see with the addition of angiogenesis inhibitors?
People have tried to improve upon the platinum-doublet regimen, and the first big improvement was published several years ago, which was adding bevacizumab to carboplatin/paclitaxel. That made great news at the time and generated great excitement, because the addition of the antiangiogenic/anti-VEGF agent improved the median overall survival (OS), progression-free survival, the 1-year OS, and we saw numbers with a median survival of greater than 1 year which we had not seen in these studies.
Bevacizumab was the first successful strategy to improve upon the platinum-based doublet. Other strategies included adding other agents targeting the blood vasculature, another monoclonal antibody targeting the VEGF-2 receptor, and a small molecular tyrosine kinase inhibitor (TKI) targeting angiogenic pathways.
For patients who are EGFR wild-type, targeting EGFR has been a strategy applied in NSCLC. We have some modest activity with TKIs and we have 1 drug that is FDA approved, which is a monoclonal antibody targeting the EGFR receptor.
Bevacizumab is a drug with promise across multiple tumor types. What impact have you seen it have in lung cancer?
In general, angiogenesis is a valid pathway. One of the challenges with getting big improvements is that we don’t have a biomarker, so we don’t have a way to select patients for it.